This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Macromolecular Crystallography of Therapeutic Proteins - Vitae Pharmaceuticals uses a structure-based drug discovery approach to produce therapeutic small molecules against protein targets to arrest or modify disease states for the benefit of the patient. This approach requires high resolution atomic structures of protein:ligand complexes which can only be obtained at this time by single-crystal X-ray methods. The NSLS offers unique capabilities to achieve these goals by providing high-intensity, tunable x-rays and the equipment needed to allow for the accurate collection of the diffracted intensities necessary to solve the underlying structures. The addition of cryogenic cooling, auto-samplers and micro-beam focussing, helps us collect good quality data from sub-optimal crystals.